The goal of this clinical research effort is to understand how the human central nervous system processes pain information and to identify abnormalities in CNS pain processing in patients with neuropathic and/or chronic pain conditions. High resolution (a) positron emission tomography (PET) with radioactive tracers or (b) functional magnetic resonance imaging (fMRI) techniques are used to assess regional brain activity via blood flow changes. These methods allow us to employ state of the art functional and structural brain imaging techniques to the study of normal and pathological pain states in human beings. a normal volunteer study involved a fully quantitative evaluation of regional cerebral blood flow during acute capsaicin induced pain. We discovered that capsaicin induced a massive decrease in global blood flow. This decrease (30%) could not be accounted for by changes in arterial pC02, heart rate or respiratory rate. This pain induced decrease is a new and previously unreported alteration in cerebral blood flow induced by a physiological stimulus. It is rapid in onset, large in magnitude, transient in duration, and may represent a novel cerebrovascular regulatory mechanism evoked by strong acute pain. Our PET studies of chronic pain associated with post-herpetic neuralgia (PHN) suggest that pain induces activity in a network of brain regions containing both nociceptive and non-nociceptive somatosensory components. The multislice fMRI studies investigated the influence of increasing levels of activation on the spatial distribution of the fMRI signals. Our data suggest that we can discriminate large versus small caliber vessels based on MR signal magnitude, although several alternative explanations need to be explored as well. MRI provides a powerful new tool for investigation of dynamic aspects of human pain and its disorder.